The mouse study, published in Science Translational Medicine, provides experimental evidence that our native microbes contribute to the mechanism that closes the blood-brain barrier before birth, and also supports previous observations that shifts in gut microbiota can impact brain development and function.
The international interdisciplinary research team, led by researchers at Sweden's Karolinska Institutet together with colleagues in Singapore and the United States, demonstrated that the transport of molecules across the blood-brain barrier can be influenced by gut microbes - which therefore play an important role in the protection of the brain.
"We showed that the presence of the maternal gut microbiota during late pregnancy blocked the passage of labelled antibodies from the circulation into the brain parenchyma of the growing foetus", explained first author Dr Viorica Braniste from the Karolinska Institutet.
"In contrast, in age-matched foetuses from germ-free mothers, these labelled antibodies easily crossed the blood-brain barrier and was detected within the brain parenchyma".
According to the researchers, the findings provide experimental evidence that alterations of our indigenous microbiota may have far-reaching consequences for the blood-brain barrier function throughout life.
"These findings further underscore the importance of the maternal microbes during early life and that our bacteria are an integrated component of our body physiology,” added senior researcher Professor Sven Pettersson.
"Given that the microbiome composition and diversity change over time, it is tempting to speculate that the blood-brain barrier integrity also may fluctuate depending on the microbiome,” he said.
Study details
The team compared the integrity and development of the blood-brain barrier between two groups of mice: the first group was raised in an environment where they were exposed to normal bacteria, and the second (called germ-free mice) was kept in a sterile environment without any bacteria.
Their findings also showed that the increased 'leakiness' of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood.
Interestingly, this 'leakiness' could be reversed if the mice were exposed to faecal transplantation of normal gut microbes, said the team.
However, they noted that the precise molecular mechanisms behind the interaction between gut bacteria and the blood-brain barrier remain to be identified.
Despite a lack of overall mechanism, the team was able to show that tight junction proteins - which are known to be important for the blood-brain barrier permeability - did undergo structural changes and had altered levels of expression in the absence of bacteria.
“This knowledge may be used to develop new ways for opening the blood-brain-barrier to increase the efficacy of the brain cancer drugs and for the design of treatment regimes that strengthens the integrity of the blood-brain barrier,” said Pettersson.
Source: Science Translational Medicine
Volume 6, Issue 263, Pages 263ra158, doi: 10.1126/scitranslmed.3009759
"BLOOD-BRAIN BARRIER: The gut microbiota influences blood-brain barrier permeability in mice"
Authors: Viorica Braniste, Maha Al-Asmakh, et al